1. Field of the Invention
The present invention relates generally to compounds, compositions and methods for the diagnosis and therapy of diseases in warm-blooded animals (e.g., in humans) involving infections with and colonization by Pseudomonas bacteria, including Pseudomonas aeruginosa in the lungs of patients with cystic fibrosis. The invention relates more particularly to the use of one or more compounds selective for binding PA-IL and/or PA-IIL lectins of Pseudomonas bacteria. These compounds are useful for diagnosis and/or therapeutic intervention of the colonization of Pseudomonas bacteria, or may be linked to an agent(s) to target and effectively arrest or kill Pseudomonas bacteria.
2. Description of the Related Art
Pseudomonas infections occur in a variety of medical conditions and can be life threatening. Pseudomonas is an opportunistic bacterium. Examples of individuals at risk include cystic fibrosis patients, burn patients, and patients on ventilators. Cystic fibrosis is described below as a representative example of a medical condition which can involve infection with Pseudomonas bacteria.
Cystic Fibrosis (CF) is the most common lethal genetic disease among the Caucasian population. CF is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), which acts as a chloride channel. The genetic mutations of CFTR which alter ion movements also affect the N-glycosylation of CFTR as well as other cell surface molecules. All of the exocrine glands of the patients are affected; however, the lungs are the primary site of morbidity and mortality. The general change in glycosylation is associated with an increase in infectivity by Pseudomonas aeruginosa. The salivary and respiratory mucins from CF patients also contain altered glycosylation patterns.
The major cause of morbidity and mortality in CF patients is chronic lung colonization by the bacterium, Pseudomonas aeruginosa, which results in pronounced lung infection with a robust neutrophilic inflammatory response leading to destruction of the lungs and death. Colonization by P. aeruginosa initiates during the sessile phase of the bacteria in which virulence factors are secreted in concert. Two virulence factors that bind carbohydrates are lectins. These lectins, known as PA-IL and PA-IIL, bind these oligosaccharide structures with high affinity and represent a potential molecular target to block bacterial colonization. Patients that are never fully colonized by the bacteria maintain an excellent long-term prognosis. Due to the difficulties in the current approaches in the art for prevention of colonization in an individual by Pseudomonas bacteria, there is a need for improved compounds, compositions and methods.